title: Salicylate (salsalate) in patients with type 2 diabetes: a randomized trial.
abstract: BACKGROUND
  Short-duration studies show that salsalate improves glycemia in type 2 diabetes mellitus (T2DM).
  
  
  OBJECTIVE
  To assess 1-year efficacy and safety of salsalate in T2DM.
  
  
  METHODS
  Placebo-controlled, parallel trial; computerized randomization and centralized allocation, with patients, providers, and researchers blinded to assignment. (ClinicalTrials.gov: NCT00799643).
  
  
  METHODS
  3 private practices and 18 academic centers in the United States.
  
  
  METHODS
  Persons aged 18 to 75 years with fasting glucose levels of 12.5 mmol/L or less (≤225 mg/dL) and hemoglobin A1c (HbA1c) levels of 7.0% to 9.5% who were treated for diabetes.
  
  
  METHODS
  286 participants were randomly assigned (between January 2009 and July 2011) to 48 weeks of placebo (n = 140) or salsalate, 3.5 g/d (n = 146), in addition to current therapies, and 283 participants were analyzed (placebo, n = 137; salsalate, n = 146).
  
  
  METHODS
  Change in hemoglobin A1c level (primary outcome) and safety and efficacy measures.
  
  
  RESULTS
  The mean HbA1c level over 48 weeks was 0.37% lower in the salsalate group than in the placebo group (95% CI, -0.53% to -0.21%; P < 0.001). Glycemia improved despite more reductions in concomitant diabetes medications in salsalate recipients than in placebo recipients. Lower circulating leukocyte, neutrophil, and lymphocyte counts show the anti-inflammatory effects of salsalate. Adiponectin and hematocrit levels increased more and fasting glucose, uric acid, and triglyceride levels decreased with salsalate, but weight and low-density lipoprotein cholesterol levels also increased. Urinary albumin levels increased but reversed on discontinuation; estimated glomerular filtration rates were unchanged.
  
  
  CONCLUSIONS
  Trial duration and number of patients studied were insufficient to determine long-term risk-benefit of salsalate in T2DM.
  
  
  CONCLUSIONS
  Salsalate improves glycemia in patients with T2DM and decreases inflammatory mediators. Continued evaluation of mixed cardiorenal signals is warranted.
authors.affiliation: Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA. allison.goldfine@joslin.harvard.edu
authors.forename: Allison B
authors.initials: AB
authors.lastname: Goldfine
authors.forename: Vivian
authors.initials: V
authors.lastname: Fonseca
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Jablonski
authors.forename: Yii-Der Ida
authors.initials: YD
authors.lastname: Chen
authors.forename: Laura
authors.initials: L
authors.lastname: Tipton
authors.forename: Myrlene A
authors.initials: MA
authors.lastname: Staten
authors.forename: Steven E
authors.initials: SE
authors.lastname: Shoelson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012459:Salicylates / Q000008:administration & dosage* / Q000009:adverse effects; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D012459:Salicylates; C014182:salicylsalicylic acid